This invention provides a new method for preparing emulsions of fluorocarbon compounds in water and its saline solutions. These emulsions have numerous applications particularly in pharmacy. Their ability to transport oxygen makes them especially useful as a substitute for red blood corpuscles.
The possibility of using fluorinated organic compounds as a blood substitute has been under study since L. C. Clark and F. Gollan (Science 152, 1755(1966)) first succeeded in maintaining mice alive while being immersed in a fluorocarbon liquid saturated with oxygen. Because of the then demonstrated large solubility of oxygen and carbon dioxide in fluorocarbons, there has rapidly followed a succession of attempts to replace blood wholly or in part by such liquids with the purpose of making them perform the functions of transporting oxygen and eliminating carbon dioxide.
Since fluorocarbons are not miscible with blood, it is not possible to inject them as such. H. A. Sloviter and T. Kamimoto (Nature, 216, 458 (1967)) and R. P. Geyer (Federation Proceedings, 27, 952 (1968)) conceived the idea of emulsifying the fluorocarbon in water or in saline water and were thus able to obtain fluids compatible with blood. In this way the complete or partial exchange of the blood of mice or dogs could be achieved with success.
However there is still a problem to convert the fluorocarbon into an emulsion with particles sufficiently fine to avoid risk of clogging the finest capillaries. The emulsion must furthermore be stable over long periods of time and must be compatible with blood plasma or with fluids of similar structure. The dispersions are in general achieved with the aid of a surface active agent and the best results thus far have been obtained with nonionic surfactants of polymeric type derived from polyoxyethylene and polyoxypropylene, known commerically under the name PLURONIC. In particular the PLURONIC F68, stated by its commercial supplier to contain 80% ethylene oxide and 20% propylene oxide has been utilized by R. P. Geyer. A standard preparation is made by dispersing 15 to 30% of a fluorocarbon compound and 2.5 to 10% of the surfactant in a physiological saline solution having an ionic composition identical with that of blood.
The formation of such emulsions, however, requires a huge quantity of energy which is generally provided by an ultrasonic generator. The emulsion can also be obtained with a pressurized homogenizer, exemplarily of the Manton Gaulin type (See the Green Cross Corp., Offenlegungsschrift 2,114,094 dated Sept. 2, 1971). These two types of preparation make possible the obtainment of very fine-particled emulsions from which any larger particles present must be separated, as by ultracentrifugation. But these techniques are extremely difficult to carry out and have the additional disadvantage of requiring such high magnitudes of energy that some carbon-fluorine bonds are broken during the process with the resultant formation of small but significant quantities of toxic fluoride ions.
Also, when the emulsions obtained by these mechanical or ultrasonic methods are sufficiently fine, with particle size cleanly limited to less than one micron, they are invariably characterized by troublesome high viscosity. (Science, 179, 669 (1973)).
The presence of fluoride ions, whose level can reach 200 ppm in emulsions prepared by ultrasonic techniques, necessitates cumbersome subsequent purification steps. Thus the toxicity of such emulsions has been diminished by treatments with ion-exchange resins. (See L. Clark, Triangle Vol. XIII No. 2, 85-96 (1973)). The future use of fluorocarbon emulsions as blood substitutes holds promise only if a more practical method of emulsification is available which does not involve the above described disadvantages.